Products in Development
Reviewed by: HU Medical Review Board | Last reviewed: August 2018. | Last updated: November 2020
For Multiple Sclerosis (MS), the current focus for treatment and research centers around disease-modifying treatments. The are several main goals of disease-modifying treatments that are in development, and/or on the market. These include improving MS-related symptoms, reducing the frequency of exacerbations, and slowing the progression of disability. Although there are several different disease-modifying treatments on the market now, their efficacies, tolerabilities, administration routes and frequencies, common adverse effects, and pregnancy-related risks, among other characteristics, are all varied. Because of this, clinical trials and treatment research continues to be performed in pursuit of the best possible options for those with MS.1,2
How does this process work?
While it may seem like a lot is going on in the research field, it’s important to note that the journey from concept to store or pharmacy shelf is a very slow one. It can take as long as 10-15 years for a treatment to make it all the way down the “pipeline” and to those who need it. Understanding this process can also help to understand treatment development as a whole. The typical steps for a product in development are as follows:
- Animal Models and Phase I: The very beginning of this process starts by trying out small, single doses on animals and/or healthy volunteers, to ensure basic safety and tolerability
- Phase II: If Phase I is passed, the focus shifts from solely surrounding basic safety concerns to testing the safety and efficacy of the drug in the target population. The groups used in Phase II are typically mid-sized, and usually does not exceed 200-300 individuals.
- Phase III: The final step in the trial pathway is Phase III, where large numbers of individuals, usually in the thousands, are included to make a definitive assessment on the treatment in question.
- Licensing and Approval: If a treatment can make it out of the trial phase, which is often a rare feat—estimated at about 1 or 2 treatments out of every 10,000—it’s data will be presented to appropriate regulatory authorities and agencies, like the US FDA (Food and Drug Administration), to determine if it is cleared for the market, and when it can be made available.
- Phase IV: Research that takes place after the FDA approves the marketing of a new drug to identify and evaluate the long-term effects of new drugs and treatments over a longer period of time for a larger number of patients
What's happening now?
Currently, there are several treatments making their way down the pipeline that have made it to Phase II and III. These treatments can be administered orally, intravenously, or by injection, and include monoclonal antibodies, immunomodulators, immunosuppressors, and neuroprotectors. Additionally, studies investigating the use of adult stem cells for the treatment of MS and MS-treating vaccinations are also making their way through the pipeline. Regardless of the specific class or mechanism of action, the goal of many of the treatments in the pipeline is to slow down or halt the degradation of myelin, the protective coat on nerve cells, that leads to the progression of symptoms and disability seen in MS. Since the exact mechanism and cause of MS is unknown, treatment has to follow leading theories. Although this list is far from exhaustive, several of these theories have led to research centering around the following.
These include antineoplastic drugs, or anti-cancer drugs. Although MS and cancer are two different conditions, anti-cancer drugs have immunosuppressive effects. It’s this property that researchers hope will lead to a slowing of myelin degradation. Anti-cancer drugs could also block the replication of cells responsible for MS decline.3
Although some of these can be immunosuppressors, not all perform the same functions. There is much research going on currently to determine if B or T immune cells (or both) contribute to MS progression, and how they do so. Some immunomodulators can act as suppressors and lead to immune cell depletion, while others may increase or modulate immune cell numbers. Immunomodulators can also affect cytokines, which depending on the specific action, can cause proinflammatory, or anti-inflammatory effects. Many of these pathways, and the way B and T cells, cytokines, and other immune system components work together are under investigation, and are the targets or immunomodulators.3
When the brain is under high levels of stress, including inflammation and degradation of neurons, neurodegeneration can take place To mitigate some of these pathways of decline, neuromodulators are in development to protect the brain and its related neurological parts, including modulating neurotransmitter function, reducing neurotoxicity, and preserving cognitive function. Some theories suggest that neurodegradation may be more pressing when it comes to MS progression than inflammatory issues.4
This subset of treatments can fall under many of the others, but have their own mechanism of action that could be considered the most specific. Essentially, antibody clones can be created to target very specific cells and cell receptors, thus, marking certain cell types for degradation or upregulation. Research is going on currently with monoclonal antibodies that deplete B cells, inhibit proinflammatory B cell functions, and inhibit T cell proliferation, among other mechanisms.3
Vaccinations for the potential treatment, not prevention, of MS have been making their way through the investigational pipeline. One such vaccine is being tested for the treatment of both RRMS and SPMS, and involves delivering fragments of myelin basic protein (MBP) to immune system cells. This process is thought to induce the immune system to become tolerant to these proteins and not attack them. MS is an autoimmune condition, where the body mistakenly attacks itself, and MBP is thought to be a potential target of these attacks, leading to the myelin degradation present in MS. By making the immune system more tolerant to these proteins, myelin degradation may be avoided.5
Statins are a class of medication indicated for use by individuals with high cholesterol. It is thought that statins have anti-inflammatory and immunomodulatory properties, and thus, may be an effective treatment for MS. Research thus far has not come to a consensus on the efficacy of statins for the treatment of MS, however, some evidence suggests that it may be beneficial for individuals with SPMS. More research is ongoing to further investigate these relationships.6,7
Stem cell therapies
The use of stem cells for the treatment of MS is an up-and-coming area of interest. Preliminary research is promising, however, much more study is needed to determine the safety, efficacy, and best practices involved with stem cell therapy for relapsing-remitting and progressive MS. Stem cells are defined as cells that are self-dividing (have the ability to self-replicate), and are able to develop into different kinds of specialized cells. Stem cells are also capable of creating functional tissue once they differentiate, or develop, into specialized cells.
There are several theories on the potential mechanisms behind how stem cells could be beneficial for the treatment of MS. One potential option is in utilizing stem cells to reboot the body’s immune system. In this approach, the body’s immune system is destroyed or significantly reduced using medications like chemotherapy. Once the body’s immune cells are depleted, hematopoietic stem cells (which can be harvested from the same individual in advance) are reinfused back into the body where they will initiate the development of a new immune system.
Another stem cell therapy option utilizes mesenchymal stem cells (MSCs). MSCs are found in adult fat and muscle tissue, as well as in bone marrow and umbilical cord blood. These cells are more readily available than other stem cell types, and can travel easily within the body, meaning they can travel into and through the central nervous system on their own. These cells are thought to help repair tissue damage, such as the nerve damage that can come along with MS, as well as have immunomodulating (immune system-impacting) effects. Additionally, a newer approach that is still currently being developed within stem cell therapy is in utilizing induced pluripotent stem cells (iPSCs) to create a wide variety of cell types. In this approach, body cells are “reprogrammed” in a lab to differentiate, or turn into, pluripotent stem cells. These cells can then go on to turn into a wide variety of different cells and carry out numerous functions within the body. While this approach is promising, it is still in the very early stages of development.8-11
Need for PPMS and SPMS treatments
Ocrelizumab, the first treatment for both RRMS and PPMS, was approved in March of 2017.12 Until then, pertinent treatments on the market were designated for RRMS only. Due to the lack of treatment options for PPMS currently available, much research will be designated to researching dual treatments for both PPMS and RRMS, and any additional treatments for PPMS only. A similar situation is present for SPMS, where mitoxantrone, a chemotherapy drug, is one of the only treatments indicated specifically for SPMS, so there is much research underway to create disease-modifying drugs for this population as well.13 There are several treatments for these groups that have already reached Phase II or III, and are still moving along.14
Regardless of the condition, combination treatments and testing can be a tricky subject. It’s not hard to envision that two drugs could be better than one, especially if they have complementary mechanisms of action, however, there is also a possibility that two drugs can interact in unexpected ways to produce negative side effects and results, or even cancel one another out.
While combination therapies are used frequently in certain conditions, few trials have been completed or are in progress on combination therapies in MS. However, at this time, a scientific consensus on combination therapies for the treatment of MS has not been found.
Disease-modifying treatments can also have a risky safety profile, and since many of the leading MS treatments fall into this category, safety risks and concerns often overshadow benefits and potential research. This has led some researchers to explore combinations of one disease-modifying treatment with another nondisease-modifying treatment, such as vitamin D, biotin, or statins.15,16 Nonetheless, combination therapies are still a topic of investigation for MS treatments.17